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Introduction: Glioblastoma (GBM), isocitrate dehydrogenase (IDH) wild-type (IDH wt), and grade 4 astrocytomas, IDH mutant (IDH mut), are the most common and aggressive primary malignant brain tumors in adults. A better understanding of the tumor immune microenvironment may provide new biomarkers and therapeutic opportunities. Objectives: We aimed to evaluate the expression profile of 730 immuno-oncology-related genes in patients with IDH wt GBM and IDH mut tumors and identify prognostic biomarkers and a gene signature associated with patient survival. Methods: RNA was isolated from formalin-fixed, paraffin-embedded sections of 99 tumor specimens from patients treated with standard therapy. Gene expression profile was assessed using the Pan-Cancer Immune Profiling Panel (Nanostring Technologies, Inc., Seattle, WA, USA). Data analysis was performed using nSolverSoftware and validated in The Cancer Genome Atlas. In addition, we developed a prognostic signature using the cox regression algorithm (Least Absolute Shrinkage and Selection Operator). Results: We found 88 upregulated genes, high immunological functions, and a high macrophage score in IDH wt GBM compared to IDH mut tumors. Regarding IDH wt GBM, we found 24 upregulated genes in short-term survivors (STS) and overexpression of CD274 (programmed death-ligand 1, PD-L1). Immune pathways, CD45, cytotoxic, and macrophage scores were upregulated in STS. Two different prognostic groups were found based on the 12-gene signature (CXCL14, PSEN2, TNFRSF13C, IL13RA1, MAP2K1, TNFSF14, THY1, CTSL, ITGAE, CHUK, CD207, and IFITM1). Conclusion: The elevated expression of immune-oncology-related genes was associated with worse outcome in IDH wt GBM patients. Increased immune functions, CD45, cytotoxic cells, and macrophage scores were associated with a more aggressive phenotype and may provide promising possibilities for therapy. Moreover, a 12 gene-based signature could predict patients' prognosis.
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PURPOSE: The aim of this study was to determine whether different radiotherapy (RT) fractionation schemes induce disparate effects on lymphocyte and its subsets in breast cancer patients. METHODS: 60 female patients diagnosed with breast cancer were recruited in this study after receiving modified radical mastectomy and were randomly divided into two groups. One group received irradiation at a standard dose of 50 Gy in 25 fractions and the other at a dose of 40.3 Gy in 13 fractions. Both total lymphocyte count and its composition were recorded at three timepoints: right before the radiation treatment (T0), immediately after the last fraction of radiotherapy (T1) and 6 months after irradiation therapy ended (T2). RESULTS: Both groups experienced temporal lymphopenia after finishing local radiation (T1) (13F T0 vs. T1 1570.6 ± 243.9 vs. 940.6 ± 141.8, **p < 0.01; 25F T0 vs. T1 1620.5 ± 280.2 vs. 948.5 ± 274.6, **p < 0.01), while the lymphocyte count recovered at follow-up time (T2), and the cell count in the hypofractionation group (13F) was higher than the standard fraction group (25F) (13F vs. 25F 1725.6 ± 225.6 vs. 1657.5 ± 242.4, *p < 0.05). With respect to the composition of lymphocyte, we found T cell, B cell, and NK cell reacted differently to different radiotherapy protocols. CONCLUSIONS: Different RT protocols impose different impacts on immunity, leading us to further explore the optimal radiotherapy regimes to synergy with immunotherapy.